GOAL: SYSTEMATIC REVIEW OF CLINICAL COMPLICATIONS OF SICKLE CELL TRAIT (SCT) For Aim 1: A systematic review of published research articles between January 1970 and December 2011 on SCT, plus a supplemental review of literature updated for 2012-2014 is in progress. Original research articles that reported an association between SCT and any condition with clinical significance are reviewed by an expert working group. GOAL: EXPLORING THE MICROBIOME AND ENVIRONMENTAL CONTRIBUTIONS TO SICKLE CELL DISEASE AND LEG ULCERS Aim 2: The study of leg ulcers in sickle cell disease is ongoing As of September 1, 2016 we have recruited 90 study participants. Our goal is to recruit 300 participants. We will sample the skin microbiome from a total of 60 adult participants with ulcers (n=30) and without leg ulcers (n=30). A total of up to 40 study participants will be sampled longitudinally during the study. The second sampling will occur at least one month after the initial sampling. This will assess longitudinal stability of the microbial community in the patient cohort. Additionally, we will compare a previously published microbiome dataset from diabetic foot ulcers to SCD leg ulcers to identify microbial signatures (similarities or differences) that exist in the microbial communities present in the different ulcers, which may be important in the healing process. Aim 3: We will conduct a cross-sectional study to investigate, stress, social function, health behaviors, and quality of life indicators for each participant with the goal of identifying environmental (i.e. social, physical, and psychosocial) factors that may impact sickle cell disease and the formation and healing of leg ulcers. We will recruit an additional 140 adult SCD patients who will not have their microbiome analyzed but who will participate in all other components of the study. Aim 4: We will conduct genomic sequencing to seek to identify the role of genetic modifiers in patients with and without leg ulcers. Specifically, we will conduct exome, whole genome, or targeted sequencing in the participants to study the genetic factors responsible for variation in leg ulceration in our patient population.